August 2015, Vol 4, No 4
The Fourth Annual World Cutaneous Malignancies Congress
The Fourth Annual World Cutaneous Malignancies Congress (WCMC) took place in Seattle, WA, on July 24-25, 2015. The WCMC is a 2-day congress dedicated to informing, educating, and fostering the exchange of clinically relevant information in the field of cutaneous malignancies on topics in melanoma, basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, and cutaneous T-cell lymphoma. The following abstracts were presented at the meeting.
CATEGORY VI: Targeted therapies
Composite Assessment of Treatment Response in Patients with Locally Advanced Basal Cell Carcinoma: Sonidegib Efficacy Using 2 Sets of Response Criteria
Reinhard Dummer,1 Vernon K. Sondak,2 James Grichnik,3 Lawrence Schwartz,4 Sven Gogov,5 Tingting Yi,6 Manisha Mone,6 Aldo Trylesinki,5 Dalia Sellami,6 Michael Migden7
1University Hospital Zurich, Zurich, Switzerland; 2H. Lee Moffitt Cancer Center, Tampa, FL, USA; 3University of Miami, Miller School of Medicine, Miami, FL, USA; 4Columbia University Medical Center, New York, NY, USA; 5Novartis Pharma AG, Basel, Switzerland; 6Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 7The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Overall Survival of Metastatic Melanoma (mM) Patients Treated with High Dose IL-2 (HD IL-2) Followed by Immune Checkpoint Blockage of the CTLA-4 or the Programmed Death (PD-1/PD-L1) Pathways: Analysis of Data on the Current Use of HD IL-2
Michael K. K. Wong1; Michael A. Morse2; David F. McDermott3; Joseph Clark4; Howard Kaufman5; Gregory A. Daniels6; Hong Hua7; Sandra Aung7
1Department of Medicine, University of Southern California, Los Angeles, CA, USA; 2Duke University Medical Center, Durham, NC, USA; 3Beth Israel Deaconess Medical Center, Boston, MA, USA; 4Loyola University Medical Center, Maywood, IL, USA; 5Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA; 6University of California San Diego, Moores Cancer Center, La Jolla, CA, USA; 7Prometheus Laboratories Inc, San Diego, CA, USA
Background: The PROCLAIMSM registry (www.proclaimregistry.com), created in 2011, is the largest collection of IL-2 treated patients in the US and provides real-time insights into sequencing or combining IL-2 with new and old therapies and how this may affect patient outcomes. Previously, we reported a median overall survival (mOS) of 20 months with a median follow-up of 37 months in mM patients treated with HD IL-2 between 2007 and 2012 from a retrospective cohort. These findings led to the hypothesis that improved mOS may have been a result of subsequent salvage therapies, including checkpoint inhibitors. Objectives: To report on the analysis of survival data from 26 sites. Methods: Patients must have received at least 1 dose of HD IL-2 for this analysis. Those who received checkpoint therapy prior to HD IL-2 were excluded. Statistics and survival analysis on prospectively entered patients were performed on data sets as of March 16, 2015. Results: The mOS for the 236 patients was 18.4 months, with a median follow-up of 21.7 months. Patients were stratified into 3 groups; HD IL-2 only (n = 123), HD IL-2 followed by ipilimumab (post ipi, n = 78), and HD IL-2 followed by PD-1/PD-L1 inhibitors (post ?PD-1, n = 35). Patients in the HD IL-2 only, post ipi, and post ?PD-1 groups achieved a mOS of 14, 15.7, and 28.7 months, respectively. The estimated 12-month survival rates were 56%, 64%, and 97%, respectively. There were 10/78 (13%) and 3/35 (8.6%) posttherapy treatment-related incidences of autoimmune events in the post ipi and post ?PD-1 groups, respectively. No treatment-related deaths were reported. Conclusions: This is the first report of clinical data relating to HD IL-2 use followed by checkpoint blockage of the PD-1/PD-L1 pathway. Treatment with anti–PD-1/PD-L1 after initial therapy with HD IL-2 had significantly prolonged survival compared with patients treated with ipilimumab. Moreover, improved survival was not observed in patients treated with follow-on ipilimumab compared with patients treated only with HD IL-2. Anti–PD-1/PD-L1 therapy after HD IL-2 appears to be safe and is therapeutically active. These data support the concept of investigating IL-2 therapy in combination or sequence with newly developed immune checkpoint inhibitors.
One of the burning questions about the new agents available to treat melanoma is how best to combine and/or sequence them. A phase 1 study showed the feasibility of combining a BRAF inhibitor and a MEK inhibitor plus a programmed death-1 ligand 1 (PD-L1) inhibitor (MEDI4736). These 3 agents can [ Read More ]
Results from the phase 3 GADOLIN trial provide the first proof of efficacy for obinutuzumab in indolent non-Hodgkin lymphoma (NHL). Obinutuzumab added to standard bendamustine chemotherapy more than doubled progression-free survival (PFS) in patients with rituximab-refractory indolent lymphoma: median PFS was 29.2 months with obinutuzumab/bendamustine versus 14 months with bendamustine [ Read More ]